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Aflatoxin B1 (AFB1) produces acute or chronic deleterious health effects in humans and animals. Still, long-term effects derived from initial exposure in early-life, a critical period for colonization and development of gut microbiota, has not been fully evaluated, . particularly, effects on gut microbiota and immunity system. This study, performed under the earlyMYCO project, investigated the impact of maternal exposure to AFB1 on early-life microbiota in a mouse model. Females were fed jelly pellets containing 400 µg/kg AFB1 diluted in DMSO (treated animals n=6) or DMSO vehicle alone (control group n=6) during pregnancy and lactation. Faeces from the offspring were collected immediately after weaning and faecal DNA was extracted and purified. Bacterial taxa diversity and relative abundance were assessed by High-Throughput Sequencing performed in an Illumina Miseq® sequencer, targeting the V3 and V4 regions of the 16S rRNA gene. Operational taxonomic units (OTUs) were determined by clustering reads to 16S reference databases. A hundred and twenty-four (N=124) bacterial genera were found in both groups, 5 were only present in AFB1 treated group and 27 exclusively in control groups. A hundred and fifty-one (N=151) bacterial species were common to both groups, 15 species exclusively found in AFB1 litters and 34 species were exclusively found in control litters. Although present in both groups, Akkermansia muciniphila and Bacteroides acidifaciens were significantly higher in controls. A. muciniphila colonizes the intestinal tract in childhood and regulates mucus thickness, intestinal barrier integrity and is involved in immune modulation. B. acidifaciens participates in the metabolism of lipids and sugars and activates some cytokines and immune cell receptors. Sulfidogenic bacteria, recently related to inflammatory bowel disease, such as Desulfovibrio piger and Bilophila wadsworthia were exclusivly found in the treated litters. Early-life gut microbiome triggers the gut immune defences, but is far less stable than the adult microbiome. These preliminary results open an extensive field to further investigate the association between mycotoxins and microbiome, as the latest is increasingly recognized as a major player in a wide spectrum of diseases. This work was funded by FCT/MCTES through national funds, to earlyMYCO (PTDC/MED-TOX/28762/2017), and CESAM (UIDP/50017/2020+UIDB/50017/2020). N/A

Humans can be exposed to multiple chemicals at once from a variety of sources, and human risk assessment of multiple chemicals poses several challenges to scientists, risk assessors and risk managers and opens new avenues for research. Ingestion of food is considered a major route of exposure to many contaminants, namely mycotoxins. Mycotoxins are natural contaminants produced by fungi and its common occurrence in food poses a threat to human health, mainly to vulnerable population groups as children. Nowadays, there is an increasing evidence that mycotoxins co-contamination of food matrices is the rule, not the exception. Likewise, the growing concern about the combined effects of mycotoxins and their potential impact on human health has been reflected by the increasing number of toxicological studies on the combined toxicity of these compounds. Nevertheless, risk assessment of these toxins, still follows the conventional paradigm of single exposure and single effects, incorporating only the possibility of additivity but not taking into account the complex dynamics associated to interactions between different mycotoxins or between mycotoxins and other food contaminants. The intestinal mucosa is the first biological barrier encountered by natural toxins, and consequently, it could be exposed to high amounts of dietary toxins as mycotoxins, and consequently the assessment of the toxic effects resulting from exposure to these compounds constitutes a crucial step within mycotoxins risk assessment. The present PhD project aimed to study Portuguese children exposure to multiple mycotoxins through food consumption applying a holistic approach for risk assessment. Additionally, the present study intended to assess the impact of multiple mycotoxins exposure on intestinal mucosa. To attain these objectives, some first-line approaches were developed/applied, namely 1) development and application of new analytical techniques on mycotoxin multiple detection and quantification, 2) understand the toxicity responses upon multiple mycotoxin exposures, with especial focus on intestinal mucosa, and 3) implement new methodologies to characterize hazard and risk for children exposure to mycotoxins. The holistic approach gathered data obtained through different approaches, including the application of deterministic and probabilistic tools to the calculation of mycotoxin daily intake values, the integration of children (under 3 years old) food consumption (3-days food diary), mycotoxins occurrence in food intended for children consumption, bioaccessibility and toxicological data. Main results showed that children exposure to ochratoxin A (OTA), fumonisins, trichothecenes and zearalenone indicate no health concern for individuals exposed to these mycotoxins through consumption of breakfast cereals, processed cereal-based products and biscuits. Contrary to other, aflatoxins exposure suggested a potential health concern for the high percentiles of intake. When analysed the combined toxic effect of patulin (PAT) and OTA in the intestinal membrane integrity, the results suggested a dose level deviation with synergism at low doses and antagonism at higher doses. Given that mycotoxin concentrations in real scenarios are generally low, especial attention should be dedicated to the mixture PAT and OTA, especially for the potential consequences of loss of membrane integrity and the potential contribution to the development of intestinal diseases. The present work underlines the need to adopt a holistic approach for multiple mycotoxins risk assessment integrating data from exposure, bioaccessibility and toxicity domains in order to contribute to a more accurate risk assessment. This research was performed under the MYCOMIX project “Exploring the toxic effects of mixtures of mycotoxins in infant food and potential health impact” (PTDC/DTP-FTO/0417/2012) and CESAM Lisboa UID/AMB/50017/2013, both funded by the Fundação para a Ciência e Tecnologia (FCT), Portugal. N/A